In this work, we investigate the adaptive sliding-mode observer design problem for the selective catalytic reduction (SCR) system in diesel-engine aftertreatment systems. First, an uncertain three-state model is obtained. Two kinds of uncertainties are considered: uncertainties with slow variations and uncertainties with fast variations. For the uncertain model, an adaptive sliding-mode observer is proposed. Then, the observer gain tuning method is developed based on the stability analysis of the estimation error system. The proposed observer design method is applied to an SCR system of a medium-duty diesel engine. Experimental results and comparisons are provided to illustrate the advantages of the designed observer according to the proposed algorithm. Compared with the open-loop SCR model and the Luenburger-like observer, the proposed adaptive sliding-mode observer can achieve better performance.